Interferon has been shown to have a suppressive effect on several types of immune responses. We have recently found that injection or induction of interferon in mice causes a marked inhibition of lymphocyte recirculation. We will determine if these two general effects of interferon--immunosuppression and impaired lymphocyte recirculation--are causally related. In this respect we aim to: (1)\evaluate the impairment in lymphocyte recirculation caused by interferon, insofar as how these cells localize and migrate in vivo and adhere to endothelial cells lining the postcapillary venules allowing for entry into lymph nodes; (2)\determine if interferon can affect the generation in vivo of cytotoxic T lymphocytes (CTL) as well as their ability to recirculate; (3)\analyze the overall functional capabilities of lymphocytes after exposure to interferon; (4)\examine whether secondary release of adrenal corticosteroids can account for some of the effects of interferon; (5)\study possible mechanisms of interferon effect on lymphocyte recirculation including whether it is directly or indirectly mediated by interferon, and possible effects on cell surface sialic acid residues and cellular actin levels; (6)\evaluate the overall capacity of interferon inhibition of lymphocyte recirculation to alter the course of rejection of a subcutaneous tumor challenge; (7) analyze the effect of interferon on the cell constituents in a sequestered inflammatory response to tumor cells injected intracerebrally; (8)\examine what type of viral agents lead to interferon production in vivo; and (9)\examine the effect of concomitant infection with a virus known to induce high levels of interferon on the course of a tumor rejection. An analysis of possible deleterious effects on immune responsiveness mediated by an interferon-associated inhibition of lymphocyte recirculation is a necessary prerequisite for proper clinical therapeutic use of interferon in the treatment of malignancy and viral infections.